Comprehensive lipid mediator analysis to identify novel biomarkers of rheumatoid arthritis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17441
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Kobe University
• Principal Investigator: Akashi Kengo 神戸大学, 医学部附属病院, 医員 (60792637)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 関節リウマチ / 脂質メディエーター / 慢性炎症

Outline of Final Research Achievements

The aim was to predict treatment response and prognosis in rheumatoid arthritis patients by lipid mediator analysis, but the impact of the COVID-19 pandemic made it difficult to collect sufficient patients. Therefore, we decided to perform a comprehensive lipid mediator analysis in a murine model of chronic arthritis. At joint sites in SKG mice, not only many proinflammatory lipid mediators but also some specialized pro-resolving mediators were elevated in arthritis mice compared with control mice. ResolvinD5, one of the specialized pro-resolving mediators, suppressed T-cell and osteoclast differentiation in vitro．These results suggest that pro-resolving lipid mediators act in an inhibitory manner against arthritis.

Free Research Field

膠原病およびアレルギー内科学

Academic Significance and Societal Importance of the Research Achievements

関節リウマチ治療は飛躍的に進歩しているが、現在でも全例が寛解には至っておらず、また治療反応予測も十分とは言えない。本研究では慢性関節炎病態における炎症収束性脂質メディエーターの働きに着目し、実際にResolvinD5が、関節リウマチの病態にも関連しているT細胞や破骨細胞の分化を抑制することを証明した。今後はヒトの関節リウマチにおいて、炎症収束性脂質メディエーター測定による治療反応予測や、更には新規治療薬としての可能性についても検討したい。